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Recent rapid responses
Rapid responses are electronic letters to the editor. They enable our users to debate issues raised in articles published on bmj.com. Although a selection of rapid responses will be included as edited readers' letters in the weekly print issue of the BMJ, their first appearance online means that they are published articles. If you need the url (web address) of an individual response, perhaps for citation purposes, simply click on the response headline and copy the url from the browser window.
Displaying 1-3 out of 3 published
Observation from REMODEL trial suggests there is no rebound thrombotic effect following cessation of Dabigatran.1 However, the question of a possible pro-thrombotic state immediately following cessation of Dabigatran has been raised by others.2 Our clinical experience suggests the need for further scientific observations in this area..
Cessation of Heparin and other anti-thrombotic medications leading to rebound of pro-thrombotic activity and clusters of thrombotic events has been noted for many years. There have been concerns about a rebound effect following discontinuation of new anti-coagulants, including Factor Xa inhibitor Rivaroxaban and another oral direct thrombin inhibitor, Ximelagatran.2 In most clinical research, events were attributed to rebound hyper-coaguability if they occurred within one month of discontinuing the oral anti-coagulant.2, 3
During the last 6 months we have encountered 3 cases of arterial or venous thrombo-embolism within one month of cessation of Dabigatran. The first was in a patient aged 86 who was taking Dabigatran for primary prevention with Atrial Fibrillation (AF) who developed a right deep vein thrombosis within 2 weeks after switching back to Aspirin due to gastro-intestinal upset and worsening renal impairment. The second was in a middle aged patient taking Dabigatran for secondary prevention after recent stroke and left ventricular impairment who was in AF. This patient stopped Dabigatran due to gastro-intestinal side effects and within 2 weeks was admitted with multiple splenic and renal infarcts. The third was in a patient aged 91 who was anti-coagulated for AF; having experienced 2 previous Transient Ischaemic Attacks. The patient felt non-specifically unwell and was changing back from Dabigatran to Warfarin. Just 4 days following cessation of Dabigatran an acute right Middle Cerebral Artery territory infarct developed.
It is difficult to prove whether these events were related to rebound or resumption of events associated with the primary condition, or underlying hypercoagulability. If there is a true rebound, it raises the question of how to most safely stop Dabigatran. Further studies looking at the levels of haemostatic factors during and following cessation of Dabigatran and prospective pharmacovigilance studies may be needed to clarify this issue.
Drs Katie Thorne, Stephen Dee and Sisira Jayathissa
1. Eriksson B I, Dahl O E, Rosencher A A, Kurth C, VanDijk S P, Frostick P et al Oral Dabigatran etexalite vs. subcutaneous enoxapirin for the prevention of venous thromboembolism after total knee replacement: the REMODEL randomised trial. Journal of Thrombosis and Haemostasis 2007;5:2178-85.
2. Hermans C, Claeys D. Review of the rebound phenomenon in new anticoagulant treatments. Current medical research and opinion. 2006 Mar;22(3):471-81
3. Cundiff. D. Clinical Evidence for Rebound Hypercoagulability After Discontinuing Oral Anticoagulants for Venous Thromboembolism. Medscape J Med. 2008; 10(11): 258.
4. Hauptmann J., Pharmacokinetics of an emerging new class of anticoagulant/antithrombotic drugs. A review of small-molecule thrombin inhibitors. European journal of clinical pharmacology. Volume 57, Number 11 (2002), 751-758
Patient consent not required (patient anonymised, dead, or hypothetical).
Two editorial changes were made to this rapid response on 29 June to increase anonymisation of details.
Competing interests: Katie Thorne received funding from Boehringer Ingelheim for flights and accomodation to attend a Stroke Interest Group in Auckland.
Hutt Valley DHB, NZ, High Street, Lower Hutt, Wellington, New Zealand
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We were heartened that the BMJ has featured cardiac rhythm management in its recent editorial (1) but were disappointed that the article put a spin on hard won progress and attention that was ill informed and misleading.
The growth in attention that has turned towards cardiac rhythm problems has been in progress for at least the last 10 years and predated any drug company interest in the problem. The Arrhythmia Alliance is an excellent example where patients and health care professionals have collaborated to bring attention to a problem that is much more abstract than the blockage of an artery that can be opened with a balloon. A marker of the struggle in drawing attention away from “plumbing” to “electrics” is that even now, when both doctors and the general public see a collapse and resuscitation on television, they will still call it a heart attack and the deputy editor of the BMJ “cannot be sure what cardiac rhythm” might prompt cardiac massage and repeated defibrillation (it is ventricular fibrillation).
Over 10 years ago the outrage expressed by patients and the public that the significant illness and death associated with cardiac arrhythmia was completely ignored by the “national service framework for coronary artery disease” led to the addition of a single arrhythmia chapter(2). Other important drivers for increasing attention have been an improved understanding of how existing therapies offer benefit (warfarin is just as safe as aspirin but much more effective at preventing AF related stroke, especially in the elderly (3)) and the development of new interventions like catheter ablation which can transform people’s lives. The new drugs like dronedarone have been very disappointing in their efficacy and are rarely prescribed by heart rhythm specialists and the new anticoagulants have really had little impact on our practice or prescribing behaviour yet. The increase in mentions in the BMJ have been a reflection of how far behind we were and how much things have improved.
What is the real future for arrhythmia management? The universally consistent feedback we have from patients (through charities like the Atrial Fibrillation Association we can actually canvass patients’ opinion and be guided by it) is that they are frustrated by the length of time it takes for them to see healthcare professional with a special interest in rhythm problems. This can be a nurse, GP or cardiologist, but their interest in rhythm problems (rather than a background of management of coronary disease or other cardiac problems) makes all the difference to the help and advice they get. We hope that this will be the standard of care in the next decade that patients will come to expect.
The editor mentions that “Fabrice Muamba has become the new patron saint of arrhythmias with his doctors not far behind”. I would challenge the editor to find a single reference in the press naming or quoting the heart rhythm specialist actually looking after Mr Muamba and I would suspect that he is confusing opinions given in the press by cardiologists, with the care that has actually been delivered by the heart rhythm specialist. We would give the same advice to the editors that we give to our patients, seek referral to a heart rhythm specialist (again this could be a nurse, GP or cardiologist) before giving your opinions, albeit very entertaining and provocative ones.
1) Delamothe T. From rags to riches: the atrial fibrillation story. BMJ. 2012;344:e3871.
2) Department of Health. National Service Frameworks. Coronary Heart Disease. London:Department of Health, 2000.
3) Mant J, Hobbs FD, Fletcher K, Roalfe A, Fitzmaurice D, Lip GY, Murray E; BAFTA investigators; Midland Research Practices Network (MidReC). Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370:493-503
Competing interests: None declared
Arrhythmia Alliance, PO Box 3697, Stratford upon Avon, Warwickshire CV37 8YL
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Delamothe’s commentary on atrial fibrillation (AF) is rather confusing . Despite correctly outlining the significant burden associated with AF and the fact that it is poorly managed, he appears to suggest that any benefit conveyed to AF patients by a recent “explosion in interest” will be offset by the fact that drug and device companies may also benefit financially. This seems a rather disappointing and naive perspective.
AF is associated with significant morbidity and its pathophysiological, symptomatic and therapeutic spectrums are frequently underappreciated and/or misunderstood. The fact that AF is being increasingly diagnosed, more widely published on and is the focus of increasing research with regard to therapeutic options will go some way to rectifying these issues and should be welcomed instead of being cynically dismissed. In contemporary practice it is difficult to imagine any major novel pharmacological or device therapy, in any field of medicine, that would not require some form of industry input. In the opinion of someone involved in the clinical management of patients with AF on a daily basis, with no personal pecuniary interest in this expanding portfolio of treatment options, this “explosion” should be warmly welcomed.
 Delamothe T. From rags to riches: the atrial fibrillation story. BMJ. 2012;344:e3871.
Competing interests: None declared
Forth Valley Royal Hospital, Larbert, FK5 4WR, UK
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